We will use PET measurements of regional cerebral blood flow (BF) and metabolism to characterize the functional anatomy of familial pure depressive disease (FPDD), a subtype of unipolar major depression. We will evaluate the hypotheses that BF is increased in the left prefrontal cortex, the left amygdala, and the left medial thalamus and decreased in the caudate during the depressed phase of FPDD. To distinguish the correlates of the depressive state from trait-abnormalities that may- underlie the tendency to become depressed, we will employ a longitudinal design in -which subjects are imaged in the unmedicated-depressed, medicated-depressed (after 2 weeks of antidepressant drug treatment), medicated-remitted (after 8 weeks of treatment), and unmedicated-remitted phases (14-24 mos. after the baseline scan). Intrasubject paired comparisons of the PET scans obtained in these four phases will also be used to examine the effects of antidepressant drugs on regional blood flow and metabolism. The physiologic measurements in the primary regions of interest will be accurately assessed using PET and magnetic resonance image (MRI) data for colocation and for correction for potential anatomical differences (related to affective disease or drug treatment) using an algorithm which assesses BF and metabolism per unit volume of tissue.